Learning objectives
• To discuss the advantages of sexual dimorphism.
• To describe how sexual differentiation is achieved during embryological development.
• To describe possible causes of indeterminate sex.
• To outline the phases of gonadal development.
• To identify the main differences in gonadal function between the male and female.
• To discuss factors affecting sexual behaviour.
Introduction
Evolutionary biologists have long questioned why evolution has led to sexual dimorphism: the differentiation of the sexes into male and female forms. Hermaphroditism remains limited to lower life forms, such as the annelids (worms) and molluscs (slugs and snails), although it is widespread throughout the plant kingdom. It is widely accepted that the development of sexual reproduction increased the speed of evolution resulting in the wide diversity of life forms upon the planet. The essential characteristic of sexual reproduction is that the new individual is generated from two distinct packages of genes: half from the male gamete (spermatozoon) and half from the female gamete (oocyte). The meiotic division that produces the gametes not only halves the normal (diploid) number of chromosomes but also increases genetic variability within each chromosome by exchange of bits of homologous chromosomes (see Chapter 7). Fertilization results in the gametes combining to form a genetically unique zygote (see Chapter 6).
Sexual reproduction results in a wide diversity of genetic material within a species, enabling the species to adapt to long-term environmental changes. The advantage of this diversity is that the population is likely to be more resilient to environmental challenges. Asexual reproduction, however, allows genetic adaptation only by mutation. The question as to why higher life forms evolved a reproductive strategy involving dimorphism remains unanswered. However, mammalian gametes are morphologically different, which lessens the potential for same-sex fertilization, which is not far removed from self-sex fertilization, thus ensuring optimal mixing of genes. So the gametes have distinct male or female forms and are made in morphologically different male and female gonads which produce a distinct pattern of sex hormones.
Chapter case study
Zara and her husband, James, would very much like to know the sex of their babies and had been informed by one of their friends, who happens to be a doctor and who they met while in Africa, that they would be able to find out the sex when they have the 12-week ultrasound scan.
• When Zara informs you, her midwife, that they wish to be told the sex of the babies when the scan is performed, what do you think would be important to discuss with Zara and her husband regarding the identification of the sex of the babies?
• Are there any situations where it can be justified to identify the sex of the baby at the 12-week scan?
• What should the midwife do if a woman requests a termination of pregnancy solely because she knows the sex of her baby?
These control both the development of the distinct male and female phenotype and affect behaviour and physiology thus ensuring that the gametes have an optimal chance of delivery and that mating occurs at the optimal time for fertilization. The sex hormones also prepare the female to carry the developing embryo throughout pregnancy and to nurture it through the period of lactation and dependency.
Sexual dimorphism is genetically controlled in many animals. However, in some species, such as crocodiles and tortoises, sexual dimorphism is principally determined by environment. The temperature of incubation of the egg promotes the development of either male or female offspring. Intermediate temperatures of egg incubation result in the ratios of the sexes altering in relation to the differing temperature gradients. In birds, the female carries the ZW chromosomes and the male the ZZ chromosomes, whereas some species of fish are able to change sex during a single lifetime. Differentiation of the sexes in mammals also involves sexual dimorphism of the urinary system because the two systems are closely linked in their development.
Differentiation into male and female
In humans, differentiation into either a male or female fetus is almost always under genetic control, depending on whether the ovum is fertilized by a sperm carrying an X chromosome (gynosperm; female) or a Y chromosome (androsperm; male). However, events such as maternal pyrexia in the first trimester of pregnancy can result in abnormal cell division and development, in some cases contributing to indeterminate (ambiguous) sexual characteristics as well as other physical malformations. As in all mammals, the human female is the homogametic sex and usually carries the XX chromosome arrangement whereas the male is the heterogametic sex and carries the XY arrangement for reproductive function to be successful. Therefore, it is the sperm that determines the sex of the fetus (Fig. 5.1). Rarely, mosaic individuals (carrying a patchwork of XX and XY cells) or those individuals with mutations in genes important for sex determination may express a phenotype opposite to their karyotype leading to XX males or XY females. If a Y chromosome is present, the individual develops testes (male gonads) regardless of the number of X chromosomes. The Y chromosome is much smaller than the X chromosome. The DNA of the Y chromosome is very condensed and so incapable of synthesizing RNA (see Chapter 7). Essentially, the Y chromosome switches on or controls the other genes required for testes formation; these genes are on the other autosomal chromosomes and the X chromosome.
Fig. 5.1 Paternal genetic determination of sex in humans. Sex determination is genetically influenced by the SRY gene normally located on the Y chromosome; therefore it is fertilization by either a gynosperm or an androsperm that influences sexual dimorphism. |
The indifferent embryo
The development of the fetus, both male and female, is initially the same. The gonads are formed from the mesenchymal tissue of the genital ridge primordia which develop each side of the descending aorta. Until approximately the 4th week of gestation, the fetus is in a sexually undifferentiated state. After this phase, the differentiation process is initiated by the activation of the SRY (sex-determining region of the Y) gene, usually found only upon the Y chromosome (Sinclair et al., 1990). The SRY gene triggers a complex cascade of events leading to testicular development (Vilain, 2000) either by activating genes leading to male development or inhibiting a repressor of male development. SRY is also expressed in a number of brain structures and may be involved in sexual behaviour. If the SRY gene is not activated (even though the genotype is XY), the female morphological form will develop. Occasionally, the SRY gene may be translocated on to an X gene, so if it is activated a male morphological state may develop from an XX genotype. Other genes are involved in SRY gene activity; it seems that the ratio of these genes to SRY is more important than the absolute amount of the genes (Johnson, 2007).
Abnormal numbers of sex chromosomes are often compatible with fetal development, and therefore occur with a relatively high birth frequency (Table 5.1). The major consequence of an aberrant number of X chromosomes is infertility. If there is an additional one or more X chromosome, as in Klinefelter's syndrome (47 chromosomes, XXY), the fetus will differentiate along the male pathway, as the Y chromosome is present. The absence of a Y chromosome, as in normal female development (XX) or Turner's syndrome (45 chromosomes, X0, where 0 indicates an absent sex chromosome), will result in the fetus developing as a female.
Table 5.1 Normal and abnormal sex chromosome complements |
||||
State |
Karyotype |
Phenotype (Expressed Sex) |
Incidence per Live Births |
Notes and Effects |
Normal female |
46, XX |
Female |
||
Turner's syndrome |
45, X0 |
Female |
0.1 per 1000 females |
Females are usually short in stature, possibly with a broad chest, webbed neck, cubitus valgus (extreme outward displacement of the extended forearm) and autism. They are infertile (primary amenorrhoea) and sexually immature. Associated with younger mothers |
‘Super female’ |
47, XXX |
Female |
1.0 per 1000 |
Normal in females appearance and fertility, may be mentally retarded |
Normal male |
46, XY |
Male |
||
Klinefelter's syndrome |
47, XXY (up to four X chromosomes have been found) |
Male |
1.3 per 1000 males |
Affected males are tall and thin with long limbs and small tests. May be infertile (azoospermia) and have gynaecomastia (breast development). May be mentally retarded. More common in sons of older mothers |
‘Super male’ |
47, XYY |
Male |
1.0 per 1000 males |
Affected males tend to be tall, have reduced IQ and show ‘antisocial’ behaviour. Some studies show increased incidence (2–3%) in institutes for the criminally insane |
Sex reversed |
46, XXsxr |
Male |
1.0 per 20 000 |
Small piece of Y chromosome containing SRY gene is translocated on to an X chromosome |
The factors that activate the SRY gene remain unknown; however, its effects are orchestrated through its influence on the production of androgens. The effects of these hormones upon tissue differentiation and development result in sexual dimorphism of the male during the embryonic phase. During the embryonic phase, female form develops in the absence of endocrine activity although oestrogen is required for puberty and fertility. Therefore, a genetic male may develop female characteristics if the SRY gene is either absent or not activated (Fig. 5.2).
Fig. 5.2 Sex determination factors: activation and influence of the SRY gene. Activation of this gene instigates a number of endocrine influences that determine the male morphology. In the absence of SRY gene activation, female morphology develops under a genetic influence. |
The undifferentiated gonad
The early human embryo is bipotential at all levels of sexual differentiation. The gonads are derived from three embryonic tissue sources: the coelomic epithelium, the underlying mesenchyme and the primordial germ cells (PGCs; Fig. 5.3). The coelomic epithelium develops into the genital ridge, which is found on the medial side of the mesonephros (which develops from the mesenchyme). The primitive germ cells, which are ultimately responsible for the production of the gametes (spermatozoa and ova), originate from the yolk sac. Here, they undergo rapid mitosis before migrating from the yolk sac wall towards the genital ridge, about 4 weeks after fertilization. The genital ridges appear to produce chemotactic substances that attract the primitive germ cells, stimulating them to develop pseudopodia and undergo amoeboid movement. Colonization of the primitive gonad by the PGCs is completed during the 6th week of embryonic development. The primitive sex cords develop from the gonadal ridges into the underlying mesenchyme forming the medulla and cortex of the gonad. In the testes, the medulla develops and will go on to form Sertoli cells and the cortex regresses; this is reversed in the development of the ovary where the cells of the sex cords condense into clusters around the PGCs (oogonia) and go on to form the primordial ovarian follicles. Two sets of primitive internal genitalia begin development. Further development will follow either the male or the female route depending on the hormonal influences.
Fig. 5.3 Development of the internal genitalia. Once differentiation of the gonads has occurred, the resulting endocrine production coordinates the development of the internal genitalia. In the male, the reproductive tract is an evolutionary adaptation of a vestigial urological system. |
The development of the male morphology
Embryological development
The embryo has two sets of primitive unipotential internal genitalia, each of which has the potential to develop depending on the hormonal environment. The SRY gene and the male gonad are essential for the development of male morphology. The SRY gene stimulates the medulla of the undifferentiated gonad to develop into the testes and produce two hormones, testosterone and anti-Müllerian hormone (AMH; also known as Müllerian-inhibiting substance, MIS or Müllerian-inhibiting hormone, MIH), which promote male genital duct development. In the absence of AMH and testosterone secretion, female sexual differentiation occurs. AMH, from Sertoli cells, drives the regression of the Müllerian structures (paramesonephric ‘female’ ducts) and testosterone, from Leydig cells, stimulates development of the Wolffian (mesonephric ‘male’) ducts into the male internal genitalia, the epididymis, vas deferens and seminiferous tubules. In the absence of testosterone, the Wolffian structures regress and the Müllerian ducts continue to develop into the uterus, uterine tubes and the upper part of the vagina. Sexual differentiation along the male pathway requires active diversion, whereas differentiation into a female embryo follows an inherent pattern or ‘default pathway’. However, some genes have been recognized as important in ovarian development (Goodfellow and Camerino, 1999).
The Wolffian, or mesonephric, ducts initially develop as part of the embryological renal system. The adaptation of the mesonephric ducts to form the male morphology is a significant development in sexual dimorphism, in evolutionary terms. Sexual differentiation at this stage is very efficient; it is extremely rare for individuals to have both testicular and ovarian tissues. These true hermaphrodites often have an internal testis on one side and an ovary on the other side (or a mixed structure known as ovatestis) which may be a result of chimerism (the fusion of a male and female embryo; Strain et al., 1998).
The phenotypic sex is determined by the sexual characteristics of the individual. The external genitalia are bipotential (can become either male or female) and initially exist as a urogenital slit flanked by urethral folds, a genital swelling and a genital tubercle or bud. Steroid hormones directly influence the development of male external genitalia (unlike the female). Testosterone from the testes is converted into 5α-dihydrotestosterone (5α-DHT) within the target cells. Under the influence of this biologically more potent androgen, the tissues of the external genitalia form the penis and scrotum (Fig. 5.4). The urethral folds fuse enclosing the urethral tube to form the shaft of the penis and genital swellings fuse to form the scrotum. The genital tubercle expands to form the glans penis. The testes, like the ovaries, initially develop within the abdominal cavity but do not remain there. They descend to their normal position within the scrotal sac, suspended outside the abdominal cavity, just before or soon after birth. However, it is quite common (in ~1 in 50 live-born males) for either one or both testes to fail to descend at this time (the condition is described as cryptorchidism). Spontaneous descent usually occurs within the first year of life. Testicular damage, potentially resulting in later failure of spermatogenesis and a higher incidence of malignant tumours, occurs if the testes remain within the abdominal cavity, so the testes are surgically lowered (orchiopexy or orchidopexy) if spontaneous resolution has not occurred (Thorup and Cortes, 2009).
Fig. 5.4 Development of the external genitalia: formation of the external genitalia is hormonally influenced; absence of testosterone or functioning testosterone receptors will result in the female morphology developing regardless of genotype. (Adapted with permission from Johnson and Everitt, 1995.) |
Testosterone is also converted into oestrogens within the brain. The presence of oestrogen is believed to be responsible for differentiation of certain brain structures along a male or female pathway. This resulting difference in morphology underpins the biological explanations for behavioural patterns differing between the sexes. Male sexual activity appears to depend on the presence of testosterone above a critical threshold. Female sexual activity in the human may be cyclical in response to changes in male behaviour. There are cyclical changes in the organic acid content of vaginal secretions (derived from normal bacterial flora), which may be a mechanism of olfactory communication to the woman's sexual partner (see Chapter 4).
Puberty
The male embryo produces testosterone with a peak of about 2 ng/mL at about weeks 13–15 (Johnston, 2007). Levels fall from then but peak to about the same level about 3 months after birth. Thereafter levels fall but slowly increase from about 12 months. As in the female, puberty commences when the secretory pattern of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), under the influence of gonadotrophin-releasing hormone (GnRH), becomes mature. Initially, secretion of LH increases nocturnally which explains the pattern of nocturnal sperm emission in pubertal boys. FSH and LH orchestrate spermatogenesis within the male (see Chapter 2). At puberty, the testes increase in size as the seminiferous tubules canalize, the Sertoli cells increase in size and the germ cells resume mitotic activity. Unlike the ovarian cycle, spermatogenesis is a continuous process resulting in the production of many gametes. The testes produce testosterone from the Leydig cells, which influences the development of the male secondary sex characteristics (Box 5.1). Unlike the female, the male retains the capability of spermatogenesis indefinitely but failure to achieve copulation becomes more common with the progression of age (Corona et al., 2010) and overall production of testosterone gradually falls from the 4th decade onwards (Schill, 2001).
Box 5.1
Male secondary sex characteristics
• Enlargement of the penis
• Pubic and axillary hair growth
• Deepening of voice (due to growth of larynx)
• Masculine pattern of fat distribution
• Development of the skeletal muscle (protein anabolism)
• Secretion of skin oil glands (predisposes to acne)
• Bone growth and adolescent growth spurt (via growth hormone secretion)
• Male sexual behaviour and aggression
The development of the female morphology
Embryological development
As the X chromosome does not contain the SRY gene, the Müllerian ducts differentiate into the female internal genitalia, the uterine tubes and fimbriae, the uterus, cervix and upper two-thirds of the vagina. The undifferentiated gonad develops into the ovary; the cortex develops and the medulla regresses. This is the route of differentiation in the absence of testosterone and MIH. Female external genitalia form independently of any hormonal influences; therefore, the ovary has little endocrine activity until puberty. The genital tubercle becomes the clitoris and the urethral folds and genital swellings remain unfused, forming the labia minora and majora, respectively.
Common abnormalities
During development, the body of the uterus, cervix and upper vagina are formed by the fusion of the two Müllerian (paramesonephric) ducts. Abnormalities may range from a simple uterine septum to the complete duplication of the reproductive system (Fig. 5.5). The failure of one of the paramesonephric ducts to develop will result in a unilateral rudimentary horn.
Fig. 5.5 Abnormalities of the female reproductive tract. |
Puberty: the initiation of fertility cycles
In the female, the germ cells or oogonia cease mitotic division and enter their first meiotic division (becoming primary oocytes) and most of them die before birth so the number of oocytes a woman has is finite and determined before her birth. Meiotic division is then arrested until the oocyte is triggered to resume development. Recruitment of primordial follicles into the pool of developing follicles begins at puberty. Puberty commences with the activation of the hypothalamus to produce GnRH in a mature pattern of secretion. It is suggested that the menarche is initiated when a critical mass of body fat, which may be genetically defined, is accumulated (Frisch, 1990). GnRH stimulates the anterior pituitary to produce FSH and LH, which orchestrate the reproductive cycles in the female (see Chapter 4). The ovaries begin to produce oestrogens, which influence the development of the female secondary sex characteristics. The breasts develop, the deposition of adipose tissue is responsible for the distinct female body curvature, and the growth of hair in the axilla and genital region commences.
The menopause
The menopause (see Chapter 4) marks the end of the ability of the female to reproduce. The menstrual cycle ceases and the ovarian cycle is lost, resulting in atrophy of the ovaries. Therefore, there is a marked decrease in the amount of systemic oestrogen present in the postmenopausal woman. Modern fertility treatments can reverse the menopause to restore the menstrual cycle but not ovarian function. Hence, postmenopausal fertility treatment requires the donation of an ovum from a fertile, premenopausal woman.
Indeterminate sex
Indeterminate, or ambiguous, sexual features at birth are usually attributable to genetic abnormality, endocrine dysfunction (see Fig. 5.6) or developmental failure. In cases of ambiguous genitalia, the karyotype of the individual is assessed to determine the chromosomal sex (i.e. the presence of a Y chromosome for a male or the absence of a Y chromosome for a female regardless of the number of X chromosomes present within the karyotype).
Fig. 5.6 Aetiology of indeterminate sex at birth. (A) testicular feminization – insensitivity to androgens; (B) androgenital syndrome – excess androgens; (C) Müllerian duct syndrome – insensitivity to AMH (MIH or MIS). |
Genetic abnormalities
The aetiology of genetic disease is discussed in Chapter 7. There are genetic conditions that result in a range of variable sexual development, such as Klinefelter's syndrome and Turner's syndrome. These disorders have been useful in understanding the control of normal sexual development. In Klinefelter's syndrome (47, XXY; normal number of autosomes but two X and one Y), the testes form normally but the germ cells die as they enter meiosis so following puberty testicular structure become fibrosed and hyalinized affecting spermatogenesis (Wilstrom and Dunkel, 2008). Studies have shown that surgical sperm retrieval is possible from around 44% of men with non-mosaic Klinefelter's syndrome and when used with ICSI has resulted in the birth of infants (Fullerton et al., 2010). It is common in men with Klinefelter's syndrome to develop breast tissue (gynaecomastia) at the onset of puberty.
In Turner's syndrome (45, X0), the single X chromosome initiates development of the ovary normally. However, the oocytes die before birth and the follicular cells become atretic, causing ovarian dysgenesis. The ovary becomes extremely regressed during fetal development, forming a highly regressed streak ovary similar to a postmenopausal ovarian structure. Although there are reports of spontaneous pregnancies in Turner's syndrome (Mortensen et al., 2010), this is rare and women with Turner's syndrome usually require hormone replacement, ovum donation and IVF to become pregnant (Abir et al., 2001). Recent research suggests that a proportion of women with Turner's syndrome (who are probably genetic mosaics of 46,XX and 45,X0) may have ovarian follicles present at adolescence which could be frozen and then theoretically be utilized with assisted conception techniques at a later date to successfully conceive (Borgstrom et al., 2009).
Endocrine dysfunction
Fetal endocrine dysfunction
It is thought that about 1% of live births exhibit some degree of sexual ambiguity (Fausto-Sterling, 2002). The dissociation of gonadal and genital sex is usually due to failure of appropriate endocrine communication (Johnson, 2007). The embryonic stage of male sexual differentiation is under endocrine influence. This may be disrupted by the failure, total or partial, of production of, or response to, the necessary hormones (Fig. 5.6). Therefore, the genetic male may fail to develop male genitalia, and appear female at birth. As described previously, the gene that codes for the androgen receptor is situated on the Y chromosome and the activation of the SRY gene results in the formation of the testes, which produce testosterone. However, if the receptor is defective, the response to testosterone will be ineffectual so the Wolffian ducts will fail to develop into the male reproductive tract. The defective receptor may also be present on other tissues so the external genitalia will also be unable to respond to testosterone and the infant will appear female. AMH will continue to inhibit the growth of the female internal reproductive tract. Thus, the child will be born with the external appearance of a female but lack both male and female internal structures. The testes remain within the abdominal cavity and as a result become dysfunctional.
Sufficient amounts of testosterone may be produced, but if the target cells lack the functional androgen receptors, or if the enzyme (5α-reductase) required to convert the testosterone into 5α-DHT is lacking, then virilization will not occur. This condition is described as testicular feminization or androgen-insensitivity syndrome (AIS). The genotype is XY and the gonads develop as testes producing androgens but the external genetalia are insensitive to the androgens and so appear female. The lack of normal endocrine communication between the gonads and genitalia causes secondary or pseudo-hermaphroditism, a disparity between the gonadal sex (having testes or ovaries) and the phenotypic sex (appearing male and female).
Müllerian duct syndrome can occur if the AMH receptor is defective (persistent Müllerian duct syndrome) or if production of AMH is inadequate. Both the Wolffian and Müllerian ducts develop simultaneously, which results in the development of both the male and female internal genitalia. The baby is genetically and gonadally male but retains the female internal structures, which developed from the Müllerian ducts. Men undergoing surgery for unrelated problems are sometimes found to have an unusual development of female internal genitalia without it causing any problem.
If a female embryo is exposed to androgens during development, the internal and external genitalia may develop on the male pathway. Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease usually caused by a defect in the enzyme 21-hydroxylase, resulting in underproduction of corticosteroid synthesis and overproduction of steroid hormones, including androgens. CAH can cause early masculinization of males and causes the majority of cases of female virilization (androgenital syndrome), accounting for most cases of ambiguous genitalia at birth. In the female fetus with CAH, androgens stimulate the development of the Wolffian ducts and stimulate the external genitalia to resemble the male form. The Müllerian system remains because there is no AMH. Although the baby is genetically and gonadally female (XX with ovaries), it has the internal genitalia of both sexes and male external genitalia. With high androgen concentrations, the sex of the baby may not initially be questioned and thus the problem may be evident only because there are no testes to descend. In the 1950s and 1960s, high levels of progestogenic drugs were given to mothers who had previously had a mid-term spontaneous abortion. It was thought that the pregnancies failed because of inadequate production of progesterone. However, progestogens are androgenic and can stimulate testosterone receptors causing pharmacological virilization of the fetus (‘progestogen-induced hermaphrodites’).
In response to rulings from the European Court of Human Rights, the UK passed the Gender Recognition Act in 2004. This allows a transsexual individual to have a gender recognition certificate which means that their ‘acquired’ gender can be legally reassigned to be different to the one on their original birth certificate which was assigned at birth.
Case study 5.1 is an example of possible endocrine dysfunction.
Case study 5.1
Milly, who is 43, has had an uncomplicated third pregnancy. Following a chorionic villus sample, she was informed that her baby appeared to have a normal female karyotype. As Milly's other children are boys, she was thrilled to be expecting a daughter because she had decided that this was to be her last pregnancy, regardless of the outcome. Milly spontaneously went into labour at 39 weeks' gestation and, following a rapid and uncomplicated delivery, a 4.2-kg male infant, of normal appearance, was presented to her.
• What are the possible reasons to explain this?
• Do you think there is a need for any further investigations and, if so, what should they be?
Developmental failure
The physiological processes resulting in the development of the reproductive tracts are complex, arising from the induction and differentiation of embryonic tissue. If the tissues, such as the pronephros upon which the gonads develop, are missing, then the gonads fail to develop because essential induction factors produced by the pronephros are lacking.
Induction, differentiation and growth of tissues are also affected by several other factors. Optimal development occurs at body core temperature. Maternal pyrexia at critical stages of embryonic development may severely disrupt the process. Many pathogens produce chemicals or toxins that can also severely affect embryological development (Box 5.2). There is growing concern among environmentalists over the increasing amounts of manmade chemical pollutants within the environment (see Box 3.5, p. 66). Many of these chemicals may disrupt endocrine function in a variety of ways, not only by inhibition but also by mimicking the effects of endogenous hormones. Case study 5.2describes an example of ambiguous genitalia.
Box 5.2
Teratogens and endocrine disrupters
• Teratogens are chemical substances that are known to interfere with embryological development and so result in the manifestation of fetal abnormalities
• Teratogens may be produced by pathogens, ingested by the mother either intentionally or unintentionally, or may be present within the external environment
• Many drugs such as Thalidomide (used in the late 1950s as an antiemetic agent in early pregnancy) are now known to produce physical deformities
Case study 5.2
The midwife examines a newborn baby and is concerned over the appearance of the genitalia. Initially, the parents had been congratulated upon the birth of a daughter but on closer examination the labia appear fused and the clitoris seems unusually large and so a referral to a paediatrician is made.
• What are the possible causes for this ambiguity?
• What investigations will be performed to establish the true sex of the baby?
• Why is it important to confirm the sex of the baby before registering the birth?
• What are the implications of assigning the wrong sex at birth?
Sexual behaviour
Hormonal control of sexual dimorphism results not only in physical differences between the male and female, but also in behavioural differences. There are many brain structures that are sexually dimorphic (different in males and females). Males have slightly larger brains and tend to perform better in visuospatial skills; they tend to show more physical aggression and display more sensation-seeking and risk-taking behaviour (Craig et al., 2004). Females, however, perform better in verbal skills, memory tasks, language and emotional processing and seem to have greater communication between the two halves of the brain. The differentiation of certain brain structures, together with biochemical differences, is thought to explain the differences in sexual behaviour between the sexes. However, it is important to acknowledge that social construction also influences the development of sexual behaviour in humans (Carlson, 1998). It is generally accepted that gonadal steroids induce brain sexual dimorphism but there may also be a direct genetic influence. Testosterone acts either directly or via local conversion into oestradiol and appears to stimulate formation of neural circuits involved in masculine behaviour.
The correct assignment of sex at birth is thought to be important in gender development, sexual orientation and attitudes later in life. Young children appear to demonstrate gender-related patterns of energy expenditure, parental rehearsal, explicit sexual behaviour and attentiveness to personal appearance. It is suggested that children recognize their own gender identity by the time they are about 2.5-years old and ambiguity may have long-term developmental consequences. It is not clear whether there is any link between transsexualism and biological or social gender ambiguity.
Human sexuality is complex; sex appears to serve a social, as well as a reproductive, function. There is a wide diversity of sexual behaviour patterns within humans, ranging from complete homosexuality, to bisexuality, to complete heterosexual behaviour (see Case studies 5.3 and 5.4). Traditionally, in Western cultures, heterosexual behaviour has always been regarded as normal and any other variation as being abnormal. This assumption was based upon many animal observations where copulation appeared to be involved only in reproduction. Justification of such behavioural patterns has been strongly argued from a sociological perspective. Recently, however, there has been an increasing amount of evidence arising from biological perspectives that attempts to explain the existence of diverse sexual behaviour (Crew, 1994).
Case study 5.3
Lisa is a 20-year-old primigravida who has conceived by donor insemination. The biological father of the baby is Lisa's brother's partner and Lisa has agreed to act as a surrogate mother for the two men.
Would Lisa's care by the midwife be any different than to a women who had conceived normally?
How could the midwife include Lisa's brother and his partner in her care and facilitate the couple's preparation for parenthood?
Are there any legal considerations that Lisa needs to consider over the parenting of the child and if so how can the midwife facilitate this?
Case study 5.4
Joan and Pippa are both pregnant and present themselves to the midwives' clinic where they inform the midwife that the babies have the same biological father who is an anonymous sperm donor. Joan and Pippa are in a stable relationship and are excited over the prospect of becoming parents. How should the midwife manage this situation and how would she plan the care of both these women?
Anatomical studies have shown that there may be biological differences within certain brain structures associated with the expression of homosexual behaviour in both males and females (LeVay and Hamer, 1993). These studies can be criticized for many reasons; for instance, they are small and the differences have been demonstrated only upon post-mortem inspection. It has been questioned whether these changes might be caused by death and whether the samples studied were representative of the entire population. Many of the males studied died from AIDS-related conditions; the possibility of physical changes in the brain being affected by these conditions needs to be excluded. There does, however, seem to be a genetic predisposition to homosexuality (Hamer et al., 1993), although sexual orientation is also affected by social, familial, environmental and endocrine factors. Finding genetic differences between homosexual and heterosexual brains may increase social acceptance of homosexuals; alternatively, it could provide a pseudoscientific rationale for discrimination and homophobia.
The emergence of genetic fingerprinting has enabled the identification of parents. Many biologists formerly accepted that many animals pair bonded, reproduced and then cooperated to bring up their young, sometimes on a seasonal basis or for life. However, recent genetic studies have revealed that the offspring of many animals were conceived outside the pair-bonding arrangement. Promiscuity appears to be widespread throughout the animal kingdom. Society often portrays the human male as sexually promiscuous but studies have shown that females are six times more likely to commit adultery at the time of ovulation than during any other time of the menstrual cycle (Ridley, 1993). This has a clinical significance in relation to family history-taking because as many as one in six children may be fathered outside of a relationship. Animal studies have also revealed that some animals use sex as a means of providing social stability. Studies of the Bonobo (pygmy chimpanzee) show that sex is used as a form of greeting, bonding and submission and that a full range of sexual behaviour from homosexuality to heterosexuality is present (De Waal, 1995).
The programming of sexual behaviour may occur by endocrine organizational influences during the embryological period. However, reproductive behaviour may also be influenced by the endocrine system on a cyclical basis. Human females copulate throughout the menstrual cycle, but sexual motivation appears to increase during the ovulatory period and to decrease during the luteal phase.
Some animal studies have shown that the presence of sex steroids is required for positive sexual behaviour to be initiated. An example of this is the female rat that is receptive to the male only at certain times. During the fertile period, the female will adopt a specific position for mating called lordosis, which is induced by the presence of oestrogens and progesterone. The sex steroids also appear to make the female chemically attractive to the male by the production of pheromonal substances. Therefore, sexual behaviour in the female rat can be described in three ways:
1. Receptive: develops an ability to copulate
2. Proceptive: increase in sexual motivation
3. Attractive: physiological changes that arouse sexual interest in the male.
Some animals have a visual signal to the attractiveness component, such as the female baboon who advertises her sexual receptiveness by developing swollen genitalia. These components of female sexual behaviour are most clearly evident in animals that have an oestrus cycle, where ovulation is stimulated by copulation to maximize the chance of fertilization. In the human female, it appears that all three components are present throughout the cycle, which suggests that sexual activity in humans has evolved to have a social role. In many animals, it appears that various forms of stimuli produced by the female influence male reproductive behaviour that promotes successful reproduction. Human male sexual behaviour, however, may have developed to be more responsive to the social aspects of sex.
Key points
• Females have two X chromosomes, whereas the presence of the SRY region on the Y chromosome causes maleness. If there is an abnormal number of sex chromosomes, the presence of a Y chromosome leads to the phenotypic expression of maleness.
• If the embryo has a Y chromosome, the indifferent gonads differentiate into testes, which produce testosterone and Müllerian-inhibiting hormone. Testosterone promotes male differentiation of the internal and external genitalia. Müllerian-inhibiting hormone causes the structures that would have formed the female internal genitalia to regress.
• The endocrine changes at puberty cause development of secondary sex characteristics and the start of reproductive maturity.
• Indeterminate or ambiguous sex at birth can be due to genetic, endocrine or development problems.
• An abnormality of sex chromosome number is frequently associated with effects on fertility and mental ability.
• Sexual behaviour has been associated with endocrinology, brain development and cultural factors.
Application to practice
• Knowledge of sexual differentiation is essential in the examination of the newborn.
• Abnormalities of the sex organs and genitalia have their aetiology in the failure or dysfunctioning of the endocrine system. This may have a genetic origin or may be influenced by external factors such as pollutants.
An increasing number of individuals with restricted fertility due to genetic conditions are being offered assisted conception techniques to achieve pregnancy. The midwife must be able to support and understand the anxieties and stress related to these situations.
Annotated further reading
De Waal, F., The ape and the sushi master: cultural reflections of a primatologist. (2001) Allen Lane, London .
This book proposes an interesting theory that suggests primates learn behaviour from observing the behaviour of other older individuals. This theory may explain social and sexual behaviour that cannot be fully explained by innate or genetically influenced behaviour patterns.
Domoney, C., Psychosexual problems, Obstet Gynaecol Reproduct Med 19 (2009) 291–295.
A short review of the more common psychosexual problems seen in gynaecology clinics and approaches to their management.
Gooren, L.J.; Kruijver, F.P., Androgens and male behavior, Mol Cell Endocrinol 198 (2002) 31–40.
This article reviews sexual dimorphism and the differentiation of the male brain in response to androgens, which affects gender identity and sexual orientation, sexual functioning and spatial ability and verbal fluency.
Imperato-McGinley, J.; Zhu, Y.S., Androgens and male physiology the syndrome of 5alpha-reductase-2 deficiency, Mol Cell Endocrinol 198 (2002) 51–59.
This review examines the effects of mutations in the 5α-reductase isozymes which convert testosterone to the more potent androgen dihydrotestosterone (DHT). Affected individuals have ambiguous external genitalia at birth so they are believed to be girls and are often raised as such; however, virilization occurs at puberty, frequently with a gender role change.
Johnson, M.H., Essential reproduction. ed 6 (2007) Blackwell Science, Oxford .
An integrated and well-organized research-based textbook that explores comparative reproductive physiology of mammals, including anatomy, physiology, endocrinology, genetics and behavioural studies.
Jorge, J.C., Statistical management of ambiguity: bodies that defy the algorithm of sex classification, Int J Crit Stat 1 (2007) 19–37.
This article challenges the current management of ambiguous genetalia cases and presents an algorithm to aid diagnosis based on management of intersexuality proposed by the American Academy of Pediatrics. It also presents an analysis of case reports of individuals who underwent gender assignment in relation to specific clinical diagnoses.
Martin, C.L.; Ruble, D.N., Patterns of gender development, Annu Rev Psychol 61 (2010) 353–381.
A comprehensive theory of gender development which discusses how children recognize gender distinctions and understand stereotypes, and the emergence of prejudice and sexism and other topics related to gender using interesting examples.
Migeon, C.J.; Wisniewski, A.B., Human sex differentiation and its abnormalities, Best Pract Res Clin Obstet Gynaecol 17 (2003) 1–18.
This article reviews the presentation and management of patients affected by conditions of abnormal sex differentiation; it includes descriptions of the medical, surgical and psychological treatment options for people affected by various intersex conditions, practice points and information about relevant Internet websites and patient support groups.
Mobler, M.; Frazer, L., Donor insemination guide: written by and for lesbian women. (2002) Parker Press, Harrington .
This guide provides an insight into same-sex parents and the use of donor insemination.
Sinha, A.; Palep-Singh, M., Taking a sexual history, Obstet Gynaecol Reproduct Med 18 (2007) 49–50.
A succinct guide about the importance of, and approaches to, taking a sexual history which focuses on sensitive topics and aspects of sexual concern.
Studd, J.; Schwenkhagen, A., The historical response to female sexuality, Maturitas 63 (2009) 107–111.
A fascinating history of medical attitudes to normal female sexual development and female sexuality.
Sykes, B., Adam's curse: a future without men. (2003) Bantam Press, London .
Written by Brian Sykes, Professor of Human Genetics at the University of Oxford, this book explores the biological and behavioural mysteries of the male sex and discusses the cannibalization of the Y chromosome by the X chromosome drawing the conclusion that men are headed for extinction.
Wilhelm, D.; Palmer, S.; Koopman, P., Sex determination and gonadal development in mammals, Physiol Rev 87 (2007) 1–28.
A comprehensive review of the biological consequences of fertilization with either an X or a Y chromosome from the sperm and the different journeys of male and female fetal development which describes the molecular and cellular events (differentiation, migration, proliferation, and communication) that distinguish testis and ovary and the changes in gene regulation underlying these two pathways.
Wylie, K.; Mimoun, S., Sexual response models in women, Maturitas 63 (2009) 112–115.
A short and useful description of a number of models which have been developed to understand the female sexual response.
References
Abir, R.; Fisch, B.; Nahum, R.; et al., Turner's syndrome and fertility: current status and possible putative prospects, Hum Reprod Update 7 (2001) 603–610.
Borgstrom, B.; Hreinsson, J.; Rasmussen, C.; et al., Fertility preservation in girls with turner syndrome: prognostic signs of the presence of ovarian follicles, J Clin Endocrinol Metab 94 (2009) 74–80.
Carlson, N.R., The physiology of behaviour, In: (1998) Allyn & Bacon, Boston, pp. 290–323.
Corona, G.; Lee, D.M.; Forti, G.; et al., Age-related changes in general and sexual health in middle-aged and older men: results from the European Male Ageing Study (EMAS), J Sex Med 7 (2010) 1362–1380.
Craig, I.W.; Harper, E.; Loat, C.S., The genetic basis for sex differences in human behaviour: role of the sex chromosomes, Ann Hum Genet 68 (2004) 269–282.
Crew, D., Animal sexuality, Sci Am 271 (1) (1994) 96–102.
De Waal, F.B.M., Bonobo sex and society, Sci Am 272 (3) (1995) 82–88.
Fausto-Sterling, A., Gender identification and assignment in intersex children, Dialog Pediatr Urol 25 (6) (2002) 4–5.
Fullerton, G.; Hamilton, M.; Maheshwari, A., Should non-mosaic Klinefelter syndrome men be labelled as infertile in 2009? Hum Reprod 25 (2010) 588–597.
Frisch, R.E., The right weight, body fat, menarche and ovulation, Baillières Clin Obstet Gynaecol 4 (1990) 419–439.
Goodfellow, P.N.; Camerino, G., DAX-1, an ‘antitestis’ gene, Cell Mol Life Sci 55 (1999) 857–863.
Hamer, D.H.; Hu, S.; Magnuson, V.L.; et al., A linkage between DNA markers on the X chromosome and male sexual orientation, Science 261 (1993) 321–327.
Johnson, M.H.; Everitt, B.J., Essential reproduction, In: ed 4 (1995) Blackwell Science, Oxford, p. 10.
Johnson, M.H., Essential reproduction. (2007) Blackwell, Oxford .
LeVay, S.; Hamer, D.H., Evidence for a biological influence in male homosexuality, Sci Am 270 (5) (1993) 44–49.
Mortensen, K.H.; Rohde, M.D.; Uldbjerg, N.; et al., Repeated spontaneous pregnancies in 45,X Turner syndrome, Obstet Gynecol 115 (2010) 446–449.
Ridley, M., The red queen: sex and the evolution of human nature. (1993) Penguin, London .
Schill, W.B., Fertility and sexual life of men after their forties and in older age, Asian J Androl 3 (2001) 1–7.
Sinclair, A.H.; Berta, P.; Palmer, M.S.; et al., A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif, Nature 346 (1990) 240–244.
Strain, L.; Dean, J.C.S.; Hamilton, M.P.R.; et al., A true hermaphrodite chimera resulting from embryo amalgamation after in vitro fertilization, N Engl J Med 338 (1998) 166–169.
Thorup, J.; Cortes, D., Surgical treatment and follow up on undescended testis, Pediatr Endocrinol Rev 7 (2009) 38–43.
Vilain, E., Genetics of sexual development, Annu Rev Sex Res 11 (2000) 1–25.
Wikstrom, A.M.; Dunkel, L., Testicular function in Klinefelter syndrome, Horm Res 69 (2008) 317–326.